A mutation in the PRKAR1B gene drives pathological mechanisms of neurodegeneration across species.

ABSTRACT: Protein kinase A (PKA) neuronal function is controlled by the interaction of a regulatory (R) subunit dimer with two catalytic subunits. Recently, the L50R variant in the gene encoding the RIβ subunit was identified in individuals with a novel neurodegenerative disease. However, the mechanisms driving the disease phenotype remained unknown. In this study, we generated a mouse model carrying the RIβ-L50R mutation to replicate the human disease phenotype and study its progression with age. We examined post-mortem brains of affected individuals as well as live cell cultures. Employing biochemical assays, immunohistochemistry and behavioural assessments, we investigated the impact of the mutation on PKA complex assembly, protein aggregation and neuronal degeneration. We reveal that RIβ is an a

SUBMITTER: Benjamin-Zukerman T 

PROVIDER: S-EPMC11531844 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature